Exposure to ozone, the principal component of photochemical smog, produces a heterogeneous pattern of response within the respiratory system of adults. Epidemiologic studies suggest that exposure to ozone during early childhood can have long lasting effects including decrements in small airways function. Recent experimental work by our group supports these findings. Extensive exposure (5 months) of infant rhesus monkeys (30 days old) to ozone profoundly remodeled the tracheobronchial airways to produce the features of chronic airways disease in adults: mucous cell hyperplasia, basement membrane thickening, altered epithelial innervation, smooth muscle hypertrophy, inflammatory cell infiltration, elevated baseline airway resistance, as well as loss of conducting airways. Taken together, this suggests that immature airways of infants are more susceptible to oxidant injury than are adults and that the postnatal developmental process itself is subject to perturbation by oxidant stress. Project 2 will define cellular basis of local antioxidant protective mechanisms in immature tracheobronchial airways of infants and how they are modulated by growth, development and allergic sensitization. The overall hypothesis that we will test is that the following four characteristics of immature airways contribute to the heightened susceptibility of infants to oxidant exposure: 1)immature airway geometry and cellular organization; 2) alterations in O3 deposition patterns during postnatal growth; 3) local differences in levels of cellular and extracellular antioxidants and 4) airway specific differences in ability to generate in inflammatory response. Project 2 will coordinate closely with Project 1 on defining the cellular basis of local antioxidant protective mechanisms in the tracheobronchial airways, with Project 3 on the relationship of evens in tracheobronchial airways to those in the nasal cavity, and with Project 4 on the development of a dynamic model of airway growth and development as it impacts on susceptibility of infants and young children to growth altering exposures to air pollutants allergens.